Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer.

Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C-C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resultantly, the efforts yielded a furyl arm bearing benzopyran possessing a 4-fluoro phenyl ring (position 2) (14) that manifested a magnificent antitumor profile against the Ishikawa cell lines mediated through dual inhibition of PARP and tubulin [(IC50 (PARP1) = 74 nM, IC50 (PARP2) = 109 nM) and tubulin (IC50 = 1.4 µM)]. Further investigations confirmed the ability of 14 to induce apoptosis as well as autophagy and cause cell cycle arrest at the G2/M phase. Overall, the outcome of the study culminated in a tractable dual PARP-tubulin inhibitor endowed with an impressive activity profile against endometrial cancer.

A Profound Insight into the Structure-activity Relationship of Ubiquitous Scaffold Piperazine: An Explicative Review.

Despite extensive research in the field of drug discovery and development, still there is a need to develop novel molecular entities. Literature reveals a substantial heterocyclic nucleus named, piperazine, which shows an immense therapeutic voyage. For several decades, molecules having the piperazine nucleus have entered the market as a drug exhibiting biological potential. It was known to possess antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardioprotective, and anti-inflammatory activity with a specific basis for structural activity relationship. Thus, it is regarded as a key structural feature in most of the already available therapeutic drugs in the market. Reports also suggest that the extensive utilization of these currently available drugs having a piperazine nucleus shows increasing tolerance significantly day by day. In addition to this, various other factors like solubility, low bioavailability, cost-effectiveness, and imbalance between pharmacokinetics and pharmacodynamics profile limit their utilization. Focusing on that issues, various structural modification studies were performed on the piperazine moiety to develop new derivatives/analogs to overcome the problems associated with available marketed drugs. Thus, this review article aims to gain insight into the number of structural modifications at the N-1 and N-4 positions of the piperazine scaffold. This SAR approach may prove to be the best way to overcome the above-discussed drawbacks and lead to the design of drug molecules with better efficacy and affinity. Hence, there is an urgent need to focus on the structural features of this scaffold which paves further work for deeper exploration and may help medicinal chemists as well as pharmaceutical industries.

Unlocking the Pharmacological Potential of Benzimidazole Derivatives: A Pathway to Drug Development.

Heterocyclic molecules have fascinated a massive interest in medicinal chemistry. They are heterocyclic compounds that have gained significance due to their diverse variety of pharmacological activities. Benzimidazole is a heterocyclic compound consisting of benzene and imidazole rings. The ease of synthesis and the structural versatility of benzimidazole make it a promising scaffold for drug development. Many biological actions of benzimidazole derivatives have been well documented, including antibacterial, antiviral, anticancer, anti-inflammatory, antitubercular, and anthelmintic properties. The mechanism of action of benzimidazole derivatives varies with their chemical structure and target enzyme. This review has explored numerous methods for producing benzimidazole derivatives as well as a broad range of pharmacological activities. SAR investigations are also discussed in this review as they provide crucial details regarding the essential structural qualities that benzimidazole derivatives must have in order to be biologically active, which could aid in the rational design of new drug candidates. Benzimidazole scaffold is an exclusive structure in drug design and discovery. Many new pharmaceutical drugs containing benzimidazole are anticipated to be available within the next ten years as a result of the extensive therapeutic applications of benzimidazole and its derivatives. This review inspired many researchers to develop more biologically active compounds bearing benzimidazole, expanding the scope of finding a remedy for other diseases. From this study, we concluded that 2-substituted benzimidazole was considered more extensively by researchers.

Therapeutic Potential and Clinical Effectiveness of Quercetin: A Dietary Supplement.

Fruits and vegetables (like apples, citrus, grapes, onions, parsley, etc.) are the primary dietary sources of quercetin. In addition, isolated quercetin is also available on the market as a dietary supplement with a daily dose of up to 1000 mg/d. The objective of the present study is to explore the therapeutic potential and clinical efficacy of quercetin as a dietary supplement. The present paper highlights the safety parameters and clinical trial studies with several targets reviewed from the data available on PubMed, Science Direct, ClinicalTrails. gov, and from many reputed foundations. The results of the studies prove the unique position of quercetin in the treatment of various disorders and the possibility of using phytochemicals such as quercetin for an efficient cure. As evidenced by the numerous published reports on human interventions, it has been concluded that quercetin intake significantly improves disease conditions with minimal adverse effects.

Decoding Therapeutic Applications of Quercetin: Recent Advancements in Nanotechnological Strategies.

For centuries, people have used herbal medicine to treat a diversity of health complications and as a natural substance, they have a favourable effect on our health. Herbal ingredients can be utilized as lead molecules in the innovation and development of a new drug. Flavonoids are a class of chemical compounds with diverse phenolic structures, and they are found in a wide variety of foods, including fruits, vegetables, cereals, bark, roots, stems, flowers, tea, and wine. Quercetin is the most prevalent polyphenolic bioflavonoid or flavonoid. Quercetin is found in many food products and has demonstrated a wide range of pharmacological activities, including the treatment of allergies, ocular diseases, metabolic ailments, inflammatory illnesses, cardiovascular ailments and arthritis. Quercetin has attracted interest as an emerging pharmacophore with the potential to significantly advance research and the development of novel therapeutic medicines for a variety of diseases. Despite having a huge therapeutic potential, these flavonoids have unfavourable pharmacokinetic characteristics, low bioavailability, and poor solubility, limiting their application in therapeutics. The objective of the current study is to present a new update on the major therapeutic uses of quercetin and other types of nanocarriers that contain quercetin to treat various ailments.

Pulegone: An Emerging Oxygenated Cyclic Monoterpene Ketone Scaffold Delineating Synthesis, Chemical Reactivity, and Biological potential.

Pulegone ((R)-5-Methyl-2-(1-methylethylidine) cyclohexanone) is a pharmacologically active, natural monoterpene ketone obtained from leaves and flowering tops of the mint family (Lamiaceae). The aim is to comprise the physicochemical and biological aspects of pulegone. All significant databases were collected via electronic search using Pubmed, Scopus, Web of Science, and Science Direct and were compiled. This review presents the occurrence, chemistry, and modifications of pulegone structure and its effect on the biological system. Pulegone represents various pharmacological properties, i.e., antioxidant, antimicrobial, anti-feeding, antifungal, antiviral, and pesticide activities, and has a significant role as an abortifacient and emmenagogue. Thus, this present review concludes the knowledgeable erudition on pulegone that paves the way for further work.

Analytical Methods for Triamcinolone Acetonide: An Exploratory Literature Review.

An artificial glucocorticoid with anti-inflammatory and immunosuppressive properties is triamcinolone acetonide. It is abundantly used to treat redness, itching, and many other skin conditions like itching and psoriasis. As a result, there are several different triamcinolone acetonide formulations available. Each of these formulations must go through the correct phases of development and validation in order to identify the medications and other additives for safer use. This review article is just a representation of all the methods reported for the development and validation of triamcinolone acetonide in pure form to break down contaminants, in addition to other medications, and even in biological samples. The International Council for Harmonization (ICH) technical requirements for human use suggestions, which include a number of analytical parameters, have been followed in the validation of all the procedures. The present study also clarified the most significant drug combination.

Quercetin-based Nanoformulation: A Potential Approach for Cancer Treatment.

Nanoformulations derived from natural products are gaining popularity as a treatment option for several human diseases, including cancer, as they offer a viable alternative to conventional cancer therapies, which are often associated with numerous side effects and complications. Quercetin (Que), a plant-derived phenolic molecule, has demonstrated potential as a chemotherapeutic agent for different types of cancer. However, Que's low water solubility, instability towards antioxidants, low bioavailability, and severe biotransformation constraints make it challenging to use in vivo. Nanoparticles have emerged as a promising technology for the precise targeting of tumor cells, leading to improved efficacy and specificity in cancer therapies. In this review, the impact of flavonoid nanoformulations on enhancing the safety, therapeutic potential, and bioavailability of Que in cancer treatment is highlighted. A variety of nanoparticle types have been developed, including polymeric micelles, liposomes, PLGA nanoparticles, coencapsulation, chitosan NPs, lipid carriers, silver and gold NPs, inorganic NPs, organic metal frameworks, and biomacromolecule- based NPs, all aimed at improving the antineoplastic efficacy of Que. These nanoparticles offer several advantages, including prolonged circulation time, tumor-specific biodistribution, high encapsulation efficiency, enhanced therapeutic efficacy, and controlled release. This review provides fresh insights into the arena of drug discovery for tumor therapies by focusing on the influence of flavonoid nanoformulations on the enhancement of their safety, therapeutic, and bioavailability characteristics.

A Review of Clinical Studies Assessing the Therapeutic Efficacy of Escitalopram: A Step Towards Development.

BACKGROUND: Major depression is a debilitating, sometimes fatal disorder, deteriorating the quality of life and well-being. Escitalopram showed highly selective and dose-dependent inhibitory activity on human serotonin transport. Selective serotonin reuptake inhibitors (SSRIs) are the first-line drugs to manage major depressive disorder (MDD). OBJECTIVE: The objective of this study is to explore the therapeutic potential of escitalopram, a clinically approved drug to manage MDD and panic disorders. METHODS: It emphasizes comparative and clinical trial studies with several pharmacological targets reviewed from the data available on PubMed, Science Direct, Clinicaltrails.gov, and from many reputed foundations. RESULTS: To highlight the clinical efficacy, safety, recent development, and stable formulation of escitalopram with an increased bioavailability profile. Evidence-based on the available clinical and pharmacoeconomic data, escitalopram represents an effective first-line treatment option for MDD patients. CONCLUSION: The present review highlights the placebo-controlled clinical studies and the recent development that can be helpful for further research perspectives.

Synergistic Effect of Piperine and its Derivatives: A Comprehensive Review.

Piperine is a fascinating substance since it can be used as a biomarker in combination with other bioactive compounds or their analogues, as well as therapeutic molecules used for the healing of a variety of diseases. It displays a plentiful therapeutic potential and various health benefits when administered alone or in combination with several other drugs and/or phytochemicals. It has also been used to enhance the pharmacokinetic profile of many nutraceutical compounds like curcumin, resveratrol, quercetin, beta-carotene, barbiturates, propranolol, metformin, theophylline etc. The present review discloses the synergistic effect of piperine and its derivatives, clinical studies, and patent studies of piperine.

Hesperidin: A Potential Therapeutic Agent against COVID-19.

COVID-19, aka Coronavirus Disease 2019, triggered by new severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2, is now a public health emergency due to its rapid spread, high transmission efficiency, and severe viral pandemic that is significantly increasing the number of patients and associated deaths. Currently, no specific treatment is available for this highly contagious virus. The unavailability of effective and specific treatments and the severity of this epidemic situation potentiate medicinal chemists' in supporting new prophylactic or therapeutic interventions against COVID-19. This study discusses the therapeutic potential of hesperidin, a traditionally used herbal medicine with an exceptional safety profile. Recent studies on hesperidin advocate its promising potential in the prevention and management of COVID-19. This paper also discusses the recent clinical studies based on the previously documented antiviral activity of hesperidin. Herein, we propose the detailed preclinical and clinical manifestations of hesperidin based on its multifaceted bioactivities to develop a novel anti-COVID-19 lead.

The Mechanistic Role of Different Mediators in the Pathophysiology of Nephropathy: A Review.

Nephropathy has become the most common reason for end-stage renal disease worldwide. The progression of end-stage renal disease occurs caused by decreased glomerular filtration rate, damage to capillaries in renal glomeruli or a higher risk of cardiovascular morbidity and mortality in diabetic patients. The involvement of mechanism in the development of nephropathy via generation of AGEs, the elevation of growth factors, altered hemodynamic and metabolic factors, inflammatory mediators, oxidative stress and dyslipidaemia. The prevalence of chronic kidney disease in India will rise from 3.7 million in 1990 to 7.63 million in 2020 becoming the main cause of mortality and morbidity. The pathogenesis of nephropathy mediates by various molecules that cause alterations in the structure and function of the kidney like growth factors, endothelins, transforming growth factor (TGF-ß), and Angiotensin-converting enzymes (ACE), fibronectin and proinflammatory cytokines, mast cells and dyslipidemia. Growth factors like VEGF, IGFs, PDGF, EGFR and TGF-ß contribute to excessive extracellular matrix accumulation, together with thickening of the glomerular and tubular basement membranes and an increase in the mesangial matrix, leading to glomerulosclerosis and tubulointerstitial fibrosis. Oxidative stress and inflammation factors like TNF-α, IL-1 and IL-6 are hypothesized to play a role in the development of pathological changes in nephropathy like renal hyperfiltration and hypertrophy, thickening of the glomerular basement membrane (GBM), glomerular lesion and tubulointerstitial fibrosis. Dyslipidemia is involved in the progression of nephropathy by impaired action of lipoprotein lipase, lecithincholesterol acyltransferase (LCAT) and cholesteryl ester transferase protein (CETP) resulting in the increased level of LDL-C, Triglyceride level and decrease HDL-C that enhance macrophage infiltration, excessive extracellular matrix production and accelerate inflammation with the development of proteinuria. Interruption in the RAS, oxidative stress and dyslipidemia have yielded much better results in terms of reno-protection and progression of nephropathy. In this review, we would focus on various factors that have been shown to contribute to renal injury in many experimental models of nephropathy.

Evolving Advances in the Cosmetic Use of Probiotics and Postbiotics: Health, Regulatory and Marketing Aspects.

Ongoing development in cosmetics is increasingly making use of probiotics, which are defined as "live microorganisms with health-enhancing properties mediated through ingestion or topical application to the host". The observation that several bacterial strains augment normal processes of healthy tissue maintenance, particularly for the skin, has opened up new avenues for the use of bacterial strains in cosmetics. A principal feature of such "cosmeceuticals" is an application of increasing insight into the biochemical nature of the skin's normal microbial flora, also called its microbiome. The opportunity of manipulating the skin microbiome to address various skin disorders has revealed novel routes for treatment. The skin microbiome manipulation approaches to address various skin disorders include skin microbiome transplantation, skin bacteriotherapy, and prebiotic stimulation. Research in this field has revealed that medical outcome-targeted manipulation of skin microbiome bacterial strain makeup may significantly increase skin health and appearance. Commercial availability of probiotic skincare products is rapidly expanding worldwide due to satisfactory laboratory results and public perception of probiotics as being intrinsically more wholesome than other bioactive substances, such as synthetics. Major outcomes of probiotic use include a significant reduction in skin wrinkling, acne and other conditions adversely affecting skin appearance and healthy function. Moreover, probiotics may additionally promote normal skin hydration, resulting in a vibrant and lustrous appearance. Nevertheless, significant technical challenges remain for the full optimization of probiotics in cosmetic products. This article summarizes the evolving nature of this field and explores current probiotic research initiatives, along with regulatory aspects and significant challenges in the manufacturing of cosmetics in the context of market expansion for these products.

Hemorrhoid Disease: A Review on Treatment, Clinical Research and Patent Data.

BACKGROUND: Hemorrhoid disease (HD) is an anal-rectal ailment that is commonly painful or may be painless and causes rectal bleeding with or without prolapsing anal tissue. It is generally associated with bleeding, prolapse, pruritus, and discomfort, which results in a diminished quality of life and well-being. OBJECTIVE: To highlight the recent developments in terms of safety, clinical efficacy, and marketed formulation for the effective management of hemorrhoids. METHOD: Reported literature available on Scopus, PubMed, Science Direct, Clinicaltrails.gov, and from many reputed foundations has been studied to summarize the recent development and clinical studies for the management of hemorrhoids. RESULTS AND CONCLUSION: The high incidence of hemorrhoids obliges the development of new molecules; therefore, safe and efficient drugs to confer protection against hemorrhoids are urgently needed. This review article mainly focuses on the newer molecules to overcome hemorrhoids and also emphasizes various studies carried out in the past.

An Update on Herbal Products for the Management of Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn's Disease (CD), is a continuously increasing healthcare problem mainly characterized by chronic relapsing intestinal inflammation. The common symptoms of UC and CD include inflammation, diarrhea, abdominal pain, bleeding, and weight loss. IBD is generally caused by an interaction between genetic and environmental or microbial factors that influence the body's immune response and is responsible for digestive disorders and inflammation of the intestinal tract. However, a complete understanding of the pathophysiology and work-up of IBD is necessary to ensure appropriate treatment for the management of this complex disease. This review enlightens herbal therapeutics and drug delivery systems for the management of IBD, and thus provides new insights into this field and facilitates access to new treatments.

Imidazole: Multi-targeted Therapeutic Leads for the Management of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a multifactorial disorder coupled with an array of neuropathological mechanisms, including tau phosphorylation, Aß aggregation, metal ion deregulation, and oxidative stress, along with neuro-inflammation. The clinically available drugs for the management of AD include four acetylcholinesterase inhibitors and one glutamatergic antagonist. These agents provide only temporary relief from the symptoms by altering the neurotransmitter level in the brain. OBJECTIVE: Keeping in view the focus on research, the numerous pharmacological activities associated with the aromatic diazole heterocyclic nucleus, imidazole, triggered the medicinal chemist to develop a large number of novel anti-AD compounds targeting multiple pathological mechanisms associated with AD. These prepared analogs represent a higher potential against neurological disorders, including AD. This review article aims an ornately pronounce the therapeutic voyage of imidazole and its analogs as anti-AD. METHODS: It emphasizes the synthesized imidazole derivatives as anti-AD with multiple targets reviewed from the data available on Pubmed. RESULTS: These compounds diminish the pathophysiological aspects of AD; still, further studies are required to prove the safety and efficacy of these compounds in humans. CONCLUSION: The review aims to provide knowledge and highlight the status of this moiety in the design and development of novel drug candidates against Alzheimer's disease conditions. Thus, it paves the way for further work.

Formulation, Development, and in-vitro Evaluation of Escitalopram Fast Dissolving Tablets.

BACKGROUND: Escitalopram, a selective serotonin reuptake inhibitor (SSRI), acts by increasing the serotonin level in the brain and is used widely for the management of depression and anxiety disorders. However, the poor dissolution rate of escitalopram due to less water solubility is a consequential problem confronting the pharmaceutical industry in developing pharmaceutical dosage forms for oral delivery systems. OBJECTIVE: The present work aims to deliver a novel formulation for improving the dissolution profile and, thus, the bioavailability of escitalopram. METHODS: Fast Dissolving Tablets (FDT) are expected to enable quick drug release, which will improve the drug's dissolving profile, allowing for the initial increase in plasma concentration mandatory in an acute depression attack. The use of co-processed excipients in tablets has been shown to increase the compressibility and disintegration properties of the tablets, resulting in improved in-vitro drug release and bioavailability. As co-processed excipients, a mixture of banana powder (a natural super disintegrant with nutritional value) and microcrystalline cellulose (a highly compressible substance with good wicking and absorption capacity) was used. RESULTS: The tablets were made using a response surface, randomised central composite design, and a direct compression technique. The manufactured tablets were found to be released more than 95% of the drug within 10 minutes and showed an improved drug release profile than the available marketed formulation. CONCLUSION: After confirming in-vivo potential, the fast release formulation exhibited impressive in-vitro findings and may prove to be a boon in treating acute depression attacks.

Therapeutic Potential and Clinical Evidence of Hesperidin as Neuroprotective Agent.

BACKGROUND: Neuroprotection is preserving neural function in various neurodegenerative diseases like Alzheimer's, Huntington's, Parkinson's, and multiple sclerosis. Hesperidin, a flavanone glycoside in citrus fruits such as sweet oranges and lemons, possesses many biological effects, including neuroprotection. OBJECTIVE: The study aims to explore the neuropharmacological mechanisms and therapeutic potential of hesperidin in the management of neurodegenerative disorders. METHODS: It emphasizes comparative and clinical trial studies with a number of targets reviewed from the data available on PubMed, Science Direct, Clinicaltrails.gov, and from many reputed foundations. RESULTS: Escalating clinical evidence has established the inhibitory effect of hesperidin in the management of neurodegenerative disorders. Neuroprotective potential of hesperidin is characterized by endogenous antioxidant defence functions, improvement of neural growth factors, antineuroinflammatory activity, and apoptotic pathways. CONCLUSION: The present study highlights the beneficial neuropharmacological potential of hesperidin, including anticonvulsant, antidepressant, antioxidant, anti-inflammatory, memory, and locomotor enhancing activities.

Inflammation as a Therapeutic Target for Various Deadly Disorders: A Review.

Inflammation is the multifaceted biological response of vascular tissues against injurious stimuli such as pathogens, irritants or infection. However, when inflammation goes away, it leads to produce quite serious life-threatening diseases like Alzheimer's, rheumatoid arthritis, heart attacks, colon cancer, etc. Therefore, inflammation suddenly has become one of the hottest areas of medical research. The present review article is aimed to provide a detailed outline of the fundamental causes and the surprising relationship of inflammation in the onset of sundry diseases or illnesses. Furthermore, the role of various anti-inflammatory drugs alone and in combination with other therapeutic drugs, in alleviating the life-threatening diseases has also been discussed.

Imidazole: An Emerging Scaffold Showing its Therapeutic Voyage to Develop Valuable Molecular Entities.

OBJECTIVE: Imidazole is a heterocyclic moiety having immense biological importance. Since ancient times, the imidazole nucleus is considered to be a promising moiety in the field of chemistry. Preliminary in vitro and in vivo studies have provided valuable scientific evidence for its use. Subsequently, imidazole constitutes a new class of compounds for new drug development as the presence of this nucleus in diverse therapeutic categories viz; antimicrobial, anti-inflammatory, anticancer, immunomodulator, antiviral etc. has made it an interesting moiety for the design and development of new pharmacological agents. Thus, this review aims to summarize the reported molecular entities which were synthesized by using conventional as well as microwave processes, chemistry and biological potential of imidazole containing heterocyclic molecules while identifying potential areas of further research on imidazole. RESULTS: The review comprises literature pertaining to the evidence-based pharmacological or therapeutic potential of imidazole using published articles and worldwide databases. Various pharmacological experiments using different models exclusively proved the potential of imidazole. SUMMARY: Focusing on the discovery and development of new imidazole nucleus based molecules at a faster rate, there is a need to search previous information available in the market in the field of medicinal chemistry. Therefore, the present review aims to elaborate the therapeutic worth of imidazole and its analogs.